Rituximab Promising in Childhood Vasculitis

Treatment was steroid-sparing in Henoch-Schonlein purpura

Rituximab (Rituxan) may be a useful option for children with chronic steroid-dependent Henoch-Schonlein purpura, a small retrospective review suggested.

Among eight children with this chronic vasculitis seen at a single center from 2006 to 2014 -- of whom seven had been hospitalized at least once (median 1.5 admissions) before being treated with rituximab -- only two were subsequently hospitalized after receiving the drug, according to Randy Cron, MD, PhD, and colleagues from the University of Alabama at Birmingham.

In addition, the median oral corticosteroid dosage was 0.345 mg/kg/day prior to rituximab treatment, and 0 mg/kg/day at 6 months (range 0-0.5), 1 year (range 0-0.2), and 2 years (0 in all patients), the researchers reported online in Pediatric Rheumatology.

Henoch-Schonlein purpura is a small-vessel vasculitis that typically is characterized by non-thrombocytopenic purpura, glomerulonephritis, abdominal pain, and arthritis. While the condition is often self-limiting, some patients have required corticosteroid treatment and for a subset, the symptoms persist and recur if steroids are tapered. Those patients often have needed long-term steroids and/or immunomodulating therapy with agents such as cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil (Cellcept).

There have been only a few reports of rituximab being used for severe, life-threatening Henoch-Schonlein purpura in children with serious renal or central nervous system involvement, and although the treatment is usually well tolerated except for infusion reactions, severe adverse events have been reported with this agent, including fatal infections, serum sickness, and progressive multifocal leukoencephalopathy.

Rituximab is a monoclonal antibody that binds to CD20 on the surface of B cells, which leads to B-cell depletion. It has been used in a variety of antibody-mediated diseases such as lupus, rheumatoid arthritis, and antineutrophil cytoplasmic antibody-associated vasculitis, most often in adults. Its use in children has been limited, despite the observation that disease relapse in young patients may be as high as 40%.

To explore a possible role for rituximab in children whose vasculitis was refractory and steroid-dependent, Cron's group reviewed their center's medical records for eight children who had been on steroids for at least 6 weeks and whose disease remained active.

Rituximab was administered as two doses of 750 mg/m2 given 2 weeks apart. High-dose pulse corticosteroids were given in conjunction with the rituximab to decrease the likelihood of allergic reactions.

The cohort included five boys and three girls whose ages ranged from 2 months to 16 years. The purpura and renal involvement were present in all, gastrointestinal involvement including severe abdominal pain, iron deficiency anemia, and hematochezia were reported in seven, and arthritis in two. The gastrointestinal symptoms had been significant in seven, requiring admission.

Six had been on oral steroids for longer than 6 weeks, and six also did not respond to immunomodulators. One patient was given rituximab before trying a disease-modifying antirheumatic drug (DMARD) because of end-stage renal disease that required dialysis, while others had been on DMARDs for at least a month before being given rituximab.

Four of the children had only one round (two doses) of rituximab treatment, one had two rounds, two had three, and one had six.

In six of the children, rituximab successfully depleted B cells, resulting in prompt resolution of gastrointestinal, skin, and joint symptoms. Seven were in remission for a mean of 1 to 91 months (median 63 months), while one also underwent IVIG infusion and daily mycophenolate mofetil and therefore was not considered to be in remission.

No serious adverse events were observed.

The current report was limited by its retrospective design and small number of patients. "Nevertheless, this cohort combined with previously reported data suggest that rituximab is a promising treatment for corticosteroid-dependent chronic Henoch-Schonlein purpura, in patients with both severe and less severe refractory disease," the investigators concluded.

Prospective studies should be conducted to further explore this potential treatment, they added.

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